Toward a Cancer Drug of Fungal Origin

Abstract

Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed and potential solutions that could be pursued by researchers are highlighted.

Translating biosynthetic gene clusters into fungal armor and weaponry

“…The statins (for example, lovastatin) are efficacious antiparasitic and antifungal agents 10,11 , yet are routinely used as cholesterol-lowering drugs. Fumagillin and its analogs are used as antifungals in treatment of microsporidial diseases 12 , including honey bee colony collapse 13 , but have also shown promise in clinical trials for obesity 14 and cancer 15 . Cyclosporin A (also called cyclosporine), although touted for its immunosuppressive properties, is also a potent antifungal; both functions are achieved through targeting the same molecule, cyclophilin, in humans and fungi 16 .…”

Scaffold Diversity of Fungal Metabolites

“…The scaffolds with the chemotype V7D6X and YVGCT correspond to Palmarumycin CP3 and Palmarumycin CP4, whose cytotoxic activity has not been reported. However, their structural similarity with Palmarumycin CP1 could indicate that the compounds in the fungal metabolites data set with these scaffolds could have antibacterial, antifungal and antitumoral activities (Kornienko et al, 2015). The scaffolds with the codes 8MY2X and ROFC5 belong to new secondary metabolites isolated from Eupenicillium brefeldianum and Aspergillus fumigatus , respectively, and their biological activity has not been reported.…”

Modulation of Bax and Bcl-2 genes by secondary metabolites produced byPenicillium rubensJGIPR9 causes the apoptosis of cancer cell lines

“…The members of the fungal genus Penicillium have been utilised worldwide for the production of highly versatile cytotoxic secondary metabolites. Many of the metabolites isolated from various species of the genus Penicillium have shown promising growth-inhibitory properties against different in-vitro as well as in-vivo human cancers (Kornienko et al 2015;Koul and Singh 2017;Youssef and Alahdal 2018). Several lead compounds from terrestrial fungi are currently being used for medicinal purposes (Gomes et al 2015).…”